Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC

Abstract

BackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer.ResultsThe transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB.ConclusionsThis study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.

Multi-omics features-based machine learning method improve immunotherapy response in clear cell renal cell carcinoma

“…4d, e, and Supplementary Data S5, 7). MT2A, a member of the metallothionein gene family, was obviously upregulated in responders but barely expressed in non-responders, which is consistent with previous findings 54 , hinting at a potential immuno-predictive biomarker (Fig. 4d and Supplementary Fig.…”

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

“… 23 NCBI BioProject: PRJNA672851 PRJNA777911 PBMC scRNA-seq dataset (ICB tested patients) Deng et al. 51 Deng et al. 51 Bulk RNA-seq dataset (ICB tested patients) Liu et al.…”

Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer

“…PBMCs scRNA-seq datasets from anti-PD-1 therapy responders and non-responders were provided by Dr. Haiyang Zhang. 48 Three responders’ and three non-responders’ gene expression matrix files were independently preprocessed and integrated. The batch effect was reduced by Harmony algorithm 24 , and cell types were annotated with markers used in the previous study.…”

“…The batch effect was reduced by Harmony algorithm 24 , and cell types were annotated with markers used in the previous study. 48 6.…”

“…The batch effect was reduced by Harmony algorithm 24 , and cell types were annotated with markers used in the previous study. 48 PBMC datasets were further integrated with 69 patients' human ESCC datasets with the same workflow and analyzed.…”